US-based biopharmaceutical company Verastem has released results from an ongoing Phase I clinical trial of focal adhesion kinase (FAK) inhibitor to treat pancreatic cancer.
FAK is a non-receptor tyrosine kinase encoded by the PTK-2 gene responsible for cellular adhesion and metastatic capability in cancer.
VS-6063 (defactinib) and VS-4718 function as FAK inhibitors and are orally administrated.
The research was spearheaded by Washington University School of Medicine immunology department oncology division assistant professor of medicine David DeNardo.
The findings of the research revealed that FAK signalling triggers fibrosis, immunosuppression and PDAC progression.
It demonstrated that single-agent treatment with Verastem’s FAK inhibitor VS-4718 slows down the tumour progression, resulting in a doubling of survival within an in vivo model of human pancreatic ductal adenocarcinoma (PDAC).
The trial has also displayed reduced tumour fibrosis, and a reduced number of tumour-infiltrating immunosuppressive cells.
It was hypothetically determined that FAK inhibition on the tumour microenvironment (TME) renders PDAC tumours more sensitive to immunotherapy.
FAK inhibition has also rendered previously unresponsive in vivo models responsive to T-cell therapy and anti-PD1 antagonists.
Verastem chief scientific officer Jonathan Pachter said: "FAK signalling has been shown to be important in several carcinomas, including pancreatic tumours, but its compelling role in creating an immunosuppressive tumour microenvironment is just emerging.
"Another study recently published in Cell found that FAK inhibition can modulate certain immune cell populations, namely CD8+ T cells and Tregs, enabling an immune response that destroys tumours.
"Similarly, in the current study, we found that FAK inhibition alters tumour cell production of pro-inflammatory and immunosuppressive cytokines and reduces the tumour’s ability to avoid immune surveillance.
"Together these findings provide important support and rationale for the ongoing Phase I, dose-escalation clinical study evaluating Verastem’s FAK inhibitor VS-6063 in combination with pembrolizumab and gemcitabine in patients with pancreatic cancer."
FAK inhibitor VS-6063 is being evaluated in combination with Merck’s PD-1 inhibitor pembrolizumab and gemcitabine in a Phase I dose-escalation study to treat pancreatic cancer.